It is well documented that metabolic deactivation of prostaglandins involves the dehydrogenation of the secondary alcohol at the C.sub.15 position. See, for example, F. F. Sun et al., "Advances in Prostaglandin and Thromboxane Research," Vol. 1, p. 163 (1976), Samuelson & Bouletti, Ed., Raven Press, New York; see also Gandolfi et al., "Advances in Prostaglandin and Thromboxane Research," Vol. 1, p. 209 (1976), Samuelson & Bouletti, Ed., Raven Press, New York; Epolitti et al., Gastroenterology, 80, pp. 55-59 (1981).
Parenterally administered prostaglandins and prostaglandin analogues are subject to dehydrogenation at the C.sub.15 position due to prostaglandin 15 hydroxy dehydrogenase (PGDH). When given orally, these compounds are subject to intragastric dehydrogenation at their C.sub.15 position. Epolitti et al., cited above, report that 15(S),15-methyl PGE.sub.2 and 16,16-dimethyl PGE.sub.2 are more stable than PGE.sub.2 itself.
Gandolfi et al., cited above, disclose that 16(S),16-methyl-13-dehydro PGE.sub.2 and its isomer, 16(R),16-methyl-13-dehydro PGE.sub.2 possess potent gastric anti-ulcer properties and are not substrates for the enzyme PGDH. It is not disclosed whether these compounds would also possess improved intragastric stability. A C.sub.13 -C.sub.14 triple bond in 16-methyl or 16,16-dimethyl PGF.sub.2 results in fairly weak reactive compounds.
It is well established in the art that metabolic oxidation of the secondary alcohol at the C.sub.15 position results in a loss of activity. Introduction of methyl groups at the C.sub.15 and C.sub.16 positions results in a better stability against PGDH and against intragastric oxidation. Introduction of a C.sub.13 -C.sub.14 triple bond might result in increased stability against PGDH. It is not known whether it also results in increased intragastric stability. Moreover, introduction of a C.sub.13 -C.sub.14 triple bond may result in important loss of activity.